Respiratory disorders represent an important segment of human disease. As the pathophysiology of human lung disease is better understood, it is apparent that immune mechanisms probably participate in an integral way, not only in the protective responses against tumors and extrinsic pathogens, but also destructively in the local tissue reactions associated with interstitial lung diseases. The objectives of this research proposal are to exploit an experimental model in inbred mice, previously developed in this laboratory, for the investigation of cytolytic immune responses occuring in respiratory tissue after local immunization with allogeneic tumor cells. Experiments are designed to a) determine the effects of the route of immunization and the age of the receipient animal on the induction of cytotoxic lymphocytes in lung tissue, b) investigation of the mechanism by which the immune system enhances or suppresses cytolytic reactions in the lung, c) characterization of the lymphocytes present in lung parenchyma and systemic tissues after intrapulmonary immunization with allogeneic tumor cells, and d) development of an in vivo model of cytotoxic responses in lung specific for hapten-conjugated syngeneic lymphocytes. The results from these studies will provide direct experimental data on the cell-mediated immune responses mediated by T-lymphocytes, on the modulation of lung immune responses by suppressor cells, on the migration and trapping of antigen-reactive cells following intrapulmonary immunization, and on the pulmonary immune response to immunization with hapten-conjugated cells--an experimental model for the lysis of virally-infected cells.